高剂量噻替派和依托泊苷用于预后不良的儿童脑肿瘤治疗

High-dose thiotepa and etoposide in children with poor-prognosis brain tumors.

作者信息

Fagioli Franca, Biasin Eleonora, Mastrodicasa Luana, Sandri Alessandro, Ferrero Ivana, Berger Massimo, Vassallo Elena, Madon Enrico

机构信息

Department of Pediatrics, Regina Margherita Children's Hospital, University of Turin, Turin, Italy.

出版信息

Cancer. 2004 May 15;100(10):2215-21. doi: 10.1002/cncr.20227.

DOI:10.1002/cncr.20227

PMID:15139067

Abstract

BACKGROUND

Outcome data were analyzed for 27 patients who were affected with recurrent or newly diagnosed high-risk brain tumors and who underwent high-dose chemotherapy with triethylenethiophosphoramide (thiotepa) and etoposide in addition to autologous stem cell transplantation between May 1992 and September 2002.

METHODS

Fifteen males and 12 females (median age, 11 years) were included in the study. Twelve patients had newly diagnosed high-risk brain tumors, and 15 patients had recurrent brain tumors. The conditioning regimen consisted of thiotepa 900 mg/m2 and etoposide 1500 mg/m2 over 3 days starting on Day -5. Stem cell rescue was performed using bone marrow (BM) in 8 patients, peripheral blood stem cells (PBSCs) in 18 patients, and BM and PBSCs in 1 patient.

RESULTS

For the BM group, neutrophil (PMN) engraftment was achieved on Day +14 (median value), whereas platelet (PLT) engraftment was achieved on Day +68 (median value). One patient did not achieve PLT engraftment. For the PBSC group, the PMN engraftment was achieved on Day +10.0 (median value), and the PLT engraftment was achieved on Day +15.5 (median value). Transplantation-related toxicity (evaluated using the Bearman score) included Grade 2-3 mucositis in 16 patients, Grade 1 kidney toxicity in 6 patients, Grade 1 liver toxicity in 6 patients, and Grade 2 liver toxicity in 1 patient. Transplantation-related mortality was observed in 1 patient (3.6%), who died of Candida pneumonia. The 3-year overall survival (OS) rate was 44.6%, and the 3-year event-free survival (EFS) rate was 31%. There was a statistically significant difference in OS and EFS rates for patients who underwent ASCT and achieved complete remission compared with patients who had measurable disease.

CONCLUSIONS

The results of the current study suggest that high-dose chemotherapy followed by ASCT may be beneficial for patients who achieve complete remission before ASCT, whereas for other patients, new strategies are required.

摘要

背景

分析了1992年5月至2002年9月期间27例复发性或新诊断的高危脑肿瘤患者的数据，这些患者除接受自体干细胞移植外，还接受了大剂量的三乙烯硫代磷酰胺（噻替派）和依托泊苷化疗。

方法

本研究纳入15例男性和12例女性（中位年龄11岁）。12例患者为新诊断的高危脑肿瘤，15例患者为复发性脑肿瘤。预处理方案包括从第-5天开始的3天内给予噻替派900mg/m²和依托泊苷1500mg/m²。8例患者使用骨髓（BM）进行干细胞救援，18例患者使用外周血干细胞（PBSC），1例患者同时使用BM和PBSC。

结果

对于BM组，中性粒细胞（PMN）在第+14天（中位值）实现植入，而血小板（PLT）在第+68天（中位值）实现植入。1例患者未实现PLT植入。对于PBSC组，PMN在第+10.0天（中位值）实现植入，PLT在第+15.5天（中位值）实现植入。移植相关毒性（使用Bearman评分评估）包括16例患者出现2-3级粘膜炎，6例患者出现1级肾毒性，6例患者出现1级肝毒性，1例患者出现2级肝毒性。观察到1例患者（3.6%）发生移植相关死亡，死于念珠菌肺炎。3年总生存率（OS）为44.6%，3年无事件生存率（EFS）为31%。接受自体造血干细胞移植（ASCT）并实现完全缓解的患者与有可测量疾病的患者相比，OS和EFS率存在统计学显著差异。